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Introduction

  • 2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline
    (World's Largest Pharmaceutical Supplier)

    CAS Number: 1000339-10-5
    Stock:
    Assay: 97%

Details

CAS Number：1000339-10-5
Catalog Number: A414457
Chemcial Name:
MW(Molecular Weight)：
MF(Molecular Formula):
SMILES：

Product Details of [ 1000339-10-5 ]

CAS No. :1000339-10-5
Formula : C13H20BNO3
M.W : 249.11
SMILES Code : NC1=CC(B2OC(C)(C)C(C)(C)O2)=CC=C1OC
MDL No. :MFCD16996341
InChI Key :SCONHACZFQZWPB-UHFFFAOYSA-N
Pubchem ID :51358159

Safety of [ 1000339-10-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 1000339-10-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 6
Fraction Csp3 0.54
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 73.81
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

53.71 ??

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.2
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.58
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

0.82
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

1.14
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.15

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.89
Solubility 0.325 mg/ml ; 0.0013 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.96
Solubility 0.272 mg/ml ; 0.00109 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-3.77
Solubility 0.0422 mg/ml ; 0.000169 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

 High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

 Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

 Yes
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

 No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

 No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

 No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

 No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

 No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.26 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ?? 500
MLOGP ?? 4.15
N or O ?? 10
NH or OH ?? 5

 0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ?? MW ?? 480
-0.4 ?? WLOGP ?? 5.6
40 ?? MR ?? 130
20 ?? atoms ?? 70

 None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ?? 10
TPSA ?? 140

 0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ?? 5.88
TPSA ?? 131.6

 0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ?? MW ?? 600
-2 ?? XLOGP ?? 5
TPSA ?? 150
Num. rings ?? 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ?? 15
H-bond acc. ?? 10
H-bond don. ?? 5

 0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

2.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ?? MW ?? 350
XLOGP ?? 3.5
Num. rotatable bonds ?? 7

 No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

 2.88

Application In Synthesis of [ 1000339-10-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1000339-10-5 ]

[ 1000339-10-5 ] Synthesis Path-Downstream   1~1

  • 1
  • [ 6358-77-6 ]
  • [ 73183-34-3 ]
  • [ 1000339-10-5 ]
YieldReaction ConditionsOperation in experiment
80% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In dimethyl sulfoxide; at 80??; for 8h;Inert atmosphere; Synthesis of 2-methoxy-5-(4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline 28.12 To potassium acetate (8.9 g, 90.83 mmol), bis-(pinacolato)-diboron (8.1 g, 31.86 mmol) and bis(diphenylphosphine) ferrocene dichloropalladium (II) (0.34 g, 0.48 mmol) was added an anhydrous solution of <strong>[6358-77-6]5-bromo-2-methoxyaniline</strong> (3.22 g, 15.93 mmol) in DMSO (40 mL) under anhydrous conditions in an atmosphere of nitrogen. The mixture was stirred at 80 C. for 8 h after which time the reaction was quenched with saturated NaCl aqueous solution (30 mL) and extracted with diethyl ether (3*20 mL). The combined ether extracts were dried over magnesium sulphate, filtered and concentrated. The crude product was purified by flash column chromatography (stationary phase; silica gel 230-400 mesh, mobile phase; 9:1 hexane/ethyl acetate). All homogenous fractions were collected and reduced in volume to afford the product 28.12 as a brown syrup (3.18 g, 80%). numax (DCM)/cm-1: 2926.38, 1599.02, 1431.11, 1356.01, 1221.39, 1142.48 1H NMR (CDCl3, 400 MHz) deltaH ppm: 1.35 (12H, s, 2*C(CH3)2), 3.89 (3H, s, OCH3), 6.15 (2H, br, NH2), 7.18 (1H, d, J 8.0 Hz, ArH), 7.25 (1H, d, J 2.5 Hz, ArH), 7.29 (1H, s, ArH). 13C NMR deltac ppm: 24.5 (4*CH3), 55.1 (OCH3), 83.2 (2*C(CH3)2) 105.5 (ArCH), 113.7 (ArC), 120.6 (ArCH), 125.8 (ArCH), 135.0 (ArC), 149.7 (ArC).
30% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In dimethyl sulfoxide; at 80??; for 48h;Inert atmosphere; 2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (60a) (0303) 5-Bromo-2-methoxyaniline (500 mg, 2.48 mmol, 1.0 equiv), bis(pinacolato)diboron (691 mg, 2.72 mmol, 1.1 equiv), potassium acetate (730 mg, 7.44 mmol, 3.0 equiv) and Pd(dppf)Cl2 (54.4 mg, 74.4 mumol, 0.03 equiv) were dissolved under Argon atmosphere in 7 ml DMSO and the mixture was stirred at 80 C. for 48 h. Water was added and the aqueous layer was extracted with ethyl acetate three times. The combined organic layers were dried over magnesium sulfate, filtered and concentrated to dryness. The raw product was purified by flash chromatography; yield: 30% (184 mg). 1H NMR (300 MHz, acetone-d6): delta 7.11-7.02 (m, 2H), 6.81 (d, J=7.9 Hz, 1H), 3.84 (s, 3H), 1.29 (s, 12H).
References: [1]Patent: US2015/18566,2015,A1 .Location in patent: Paragraph 0685; 0686; 0687; 0688; 0689.
[2]Journal of Medicinal Chemistry,2015,vol. 58,p. 3767 - 3793.
[3]Patent: US2016/318895,2016,A1 .Location in patent: Paragraph 0303.
[4]Journal of Medicinal Chemistry,2018,vol. 61,p. 10724 - 10738.
 

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